The Journal of Physiological Sciences

, Volume 62, Issue 3, pp 211–219 | Cite as

Subepithelial trypsin induces enteric nerve-mediated anion secretion by activating proteinase-activated receptor 1 in the mouse cecum

  • Osamu Ikehara
  • Hisayoshi Hayashi
  • Toshiharu Waguri
  • Izumi Kaji
  • Shin-ichiro Karaki
  • Atsukazu Kuwahara
  • Yuichi Suzuki
Original Paper


Serine proteases are versatile signaling molecules and often exert this function by activating the proteinase-activated receptors (PAR1–PAR4). Our previous study on the mouse cecum has shown that the PAR1-activating peptide (AP) and PAR2-AP both induced electrogenic anion secretion. This secretion mediated by PAR1 probably occurred by activating the receptor on the submucosal secretomotor neurons, while PAR2-mediated anion secretion probably occurred by activating the receptor on the epithelial cells. This present study was aimed at using trypsin to further elucidate the roles of serine proteases and PARs in regulating intestinal anion secretion. A mucosal–submucosal sheet of the mouse cecum was mounted in Ussing chambers, and the short-circuit current (Isc) was measured. Trypsin added to the serosal side increased Isc with an ED50 value of approximately 100 nM. This Isc increase was suppressed by removing Cl from the bathing solution. The Isc increase induced by 100 nM trypsin was substantially suppressed by tetrodotoxin, and partially inhibited by an NK1 receptor antagonist, by a muscarinic Ach-receptor antagonist, and by 5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptor antagonists. The Isc increase induced by trypsin was partially suppressed when the tissue had been pretreated with PAR1-AP, but not by a pretreatment with PAR2-AP. These results suggest that the serine protease, trypsin, induced anion secretion by activating the enteric secretomotor nerves. This response was initiated in part by activating PAR1 on the enteric nerves. Serine proteases and PARs are likely to be responsible for the diarrhea occurring under intestinal inflammatory conditions.


Serine protease Inflammation Diarrhea Eicosanoid 5-Hydroxytryptamine Substance P 


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Copyright information

© The Physiological Society of Japan and Springer 2012

Authors and Affiliations

  • Osamu Ikehara
    • 1
  • Hisayoshi Hayashi
    • 1
  • Toshiharu Waguri
    • 1
  • Izumi Kaji
    • 2
  • Shin-ichiro Karaki
    • 2
  • Atsukazu Kuwahara
    • 2
  • Yuichi Suzuki
    • 1
  1. 1.Laboratory of Physiology, School of Food and Nutritional SciencesUniversity of ShizuokaSurugakuJapan
  2. 2.Laboratory of Physiology, Department of Environmental Health Sciences, Graduate School of Nutritional and Environmental SciencesUniversity of ShizuokaSurugakuJapan

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